Antibody Recognition of Cancer Cells via Glycan Surface Engineering

Stimulation of the body's immune system toward tumor cells is now well recognized as a promising strategy in cancer therapy. Just behind cell therapy and monoclonal antibodies, small molecule-based strategies are receiving growing attention as alternatives to direct immune response against tumor cells. However, the development of small-molecule approaches to modulate the balance between stimulatory immune factors and suppressive factors in a targeted way remains a challenge. Here, we report the cell surface functionalization of LS174T cancer cells with an abiotic hapten to recruit antibodies to the cell surface. Metabolic glycoengineering followed by covalent reaction with the hapten results in antibody recognition of the target cells. Microscopy and flow cytometry studies provide compelling evidence that metabolic glycoengineering and small molecule stimulators can be combined to direct antibody recognition. Keywords: antibody; bioorganic chemistry; cancer; chemical biology; glycoengineerin

On-cell catalysis by surface engineering of live cells with an artificial metalloenzyme

Metal-catalyzed chemical transformations performed at the cellular level bear great potential for the manipulation of biological processes. The complexity of the cell renders the use of transition metal chemistry difficult in cellular systems. The delivery of the reactive catalyst and the control of its spatial localization remain challenging. Here we report the surface functionalization of the unicellular eukaryote Chlamydomonas reinhardtii with a tailor-made artificial metalloenzyme for on-cell catalysis. The functionalized cells remain viable and are able to uncage a fluorogenic substrate on their surface. This work leverages cell surface engineering to provide live cells with new-to-nature reactivity. In addition, this operationally simple approach is not genetically encoded and thereby transient, which offers advantages with regard to temporal control, cell viability, and safety. Therefore, and as a feature, the movement of the functionalized cells can be directed by light (via phototaxis), allowing for the three-dimensional localization of catalysts by outside stimuli